The balance between the pro-inflammatory effect of plasma noradrenaline and the anti-inflammatory effect of neuronal noradrenaline determines the peripheral effect of noradrenaline

Perfusion experiments on an isolated, canine lateral saphenous vein segment preparation have shown that noradrenaline causes potent, flow dependent effects, at a threshold concentration comparable to that of plasma noradrenaline, when it stimulates the segment by diffusion from its microcirculation (vasa vasorum). The effects caused are opposite to those neuronal noradrenaline causes in vivo and that, in the light of the principle that all information is transmitted in patterns that need contrast to be detected – star patterns need darkness, sound patterns, quietness – has generated the hypothesis that plasma noradrenaline provides the obligatory contrast tissues need to detect and respond to the regulatory information encrypted in the diffusion pattern of neuronal noradrenaline. Based on the implications of that hypothesis, the controlled variable of the peripheral noradrenergic system is believed to be the maintenance of a set point balance between the contrasting effects of plasma and neuronal noradrenaline on a tissue. The hypothalamic sympathetic centres are believed to monitor that balance through the level of afferent sympathetic traffic they receive from a tissue and to correct any deviation it detects in the balance by adjusting the level of efferent sympathetic input it projects to the tissue. The failure of the centres to maintain the correct balance, for reasons intrinsic or extrinsic to themselves, is believed to be responsible for degenerative and genetic disorders. When the failure causes the balance to be polarised in favour of the effect of plasma noradrenaline that is believed to cause inflammatory diseases like dilator cardiac failure, renal hypertension, varicose veins and aneurysms; when it causes it to be polarised in favour of the effect of neuronal noradrenaline that is believed to cause genetic diseases like hypertrophic cardiopathy, pulmonary hypertension and stenoses and when, in pregnancy, a factor causes the polarity to favour plasma noradrenaline in all the maternal tissues except the uterus and conceptus, where it favours neuronal noradrenaline, that is believed to cause preeclampsia.

Patterns of psychotropic prescribing and polypharmacy in older hospitalized patients in Ireland: the influence of dementia on prescribing

Neuropsychiatric Symptoms (NPS) are ubiquitous in dementia and are often treated pharmacologically. The objectives of this study were to describe the use of psychotropic, anti-cholinergic, and deliriogenic medications and to identify the prevalence of polypharmacy and psychotropic polypharmacy, among older hospitalized patients in Ireland, with and without dementia. All older patients (≥ 70 years old) that had elective or emergency admissions to six Irish study hospitals were eligible for inclusion in a longitudinal observational study. Of 676 eligible patients, 598 patients were recruited and diagnosed as having dementia, or not, by medical experts. These 598 patients were assessed for delirium, medication use, co-morbidity, functional ability, and nutritional status. We conducted a retrospective cross-sectional analysis of medication data on admission for 583/598 patients with complete medication data, and controlled for age, sex, and co-morbidity. Of 149 patients diagnosed with dementia, only 53 had a previous diagnosis. At hospital admission, 458/583 patients experienced polypharmacy (≥ 5 medications). People with dementia (PwD) were significantly more likely to be prescribed at least one psychotropic medication than patients without dementia (99/147 vs. 182/436; p < 0.001). PwD were also more likely to experience psychotropic polypharmacy (≥ two psychotropics) than those without dementia (54/147 vs. 61/436; p < 0.001). There were no significant differences in the prescribing patterns of anti-cholinergics (23/147 vs. 42/436; p = 0.18) or deliriogenics (79/147 vs. 235/436; p = 0.62). Polypharmacy and psychotropic drug use is highly prevalent in older Irish hospitalized patients, especially in PwD. Hospital admission presents an ideal time for medication reviews in PwD.